Association between functional polymorphism in EGF 61 G/A gene and malignant melanoma

Immunology Research Group, School of Biological Sciences, Stopford Building, University of Manchester, Manchester M13 9PT, UK.
The Lancet (Impact Factor: 45.22). 03/2002; 359(9304):397-401. DOI: 10.1016/S0140-6736(02)07600-6
Source: PubMed


Malignant melanoma, the most serious cutaneous malignancy, has attracted substantial attention because of its rapidly increasing incidence and the poor prognosis of some tumours. Little is known of the genetic factors that mediate susceptibility to, and outcome of, sporadic malignant melanoma. Because of its role in mitogenesis, which is especially relevant to wound healing, tumorigenesis, and proliferation of epidermal tissues, epidermal growth factor (EGF) is an attractive candidate in which to look for genetic polymorphisms.
We enrolled 135 white European patients with malignant melanoma and 99 healthy white European controls, and screened a selection of DNA samples for polymorphisms in the promoter and 5' untranslated region of the EGF gene by analysis. We then screened DNA samples from all participants for the identified polymorphism by restriction-fragment-length polymorphism (RFLP) analysis. In-vitro EGF production was measured in peripheral-blood mononuclear cells from 34 controls, and the results were compared with the individuals' EGF genotypes.
We identified a single nucleotide substitution (G to A) at position 61 of the EGF gene. Allele frequencies in the controls were 56% EGF 61*A and 44% EGF 61*G. Cells from individuals homozygous for the 61*A allele produced significantly less EGF than cells from 61*G homozygotes (p=0.0004) or heterozygous A/G individuals (p=0.001). Compared with the A/A genotype, G/G was significantly associated with Breslow thickness (p=0.045) and with risk of malignant melanoma (odds ratio 4.9 [95% CI 2.3-10.2], p<0.0001).
This study suggests that high EGF production might be important in the development of malignant melanoma.

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    • "A previous analysis from northern England has shown that a marked rise in incidence was confined to females (Magnanti et al., 2008). It is well known that both genetic susceptibility and exposure to UVR are key factors in etiology (Cockburn et al., 2001; Wachsmuth et al., 2001; Shahbazi et al., 2002; El Ghissassi et al., 2009). The finding of a seasonal association between time of birth and risk of subsequently developing melanoma suggests that early life exposures may be implicated (Basta et al., 2011). "
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    Full-text · Article · Jun 2014 · Journal of Investigative Dermatology
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    • "Single nucleotide polymorphisms (SNPs) are the most common cause of human genetic alternation and may contribute in susceptibility and intensity of disease(13). Relation between EGF rs4444903 polymorphism located in 5′UTR and several cancer was investigated including, colorectal cancer (14), prostate cancer (15), melanoma (16), ovarian cancer (17) and breast cancer (18). According to our knowledge several single nucleotide polymorphisms have been identified in EGF gene region but a few study reported of EGF gene exonic polymorphisms and coloration between type of cancer (19, 20). "
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    ABSTRACT: This study aimed to determinant association between rs76189946 polymorphism of EGF gene and risk of colorectal cancer in an Iranian population. Colorectal cancer (CRC) is the third most prevalent cancer in both genders worldwide. The determination of genetic variation becomes a new way to etiology of colorectal cancer. Epidermal growth factor (EGF) is a mitogen that plays an important role in cell growth and tumourigenesis, this protein acts by binding its receptor, EGFR. DNA samples taken from totally 125 CRC patients and healthy controls were amplified by polymerase chain reaction (PCR) for the rs76189946 polymorphism. Genotypes were analyzed using restriction fragment length polymorphism (RFLP). Finally to confirm the RFLP procedure, 20 of the PCR products were sequenced using the ABI PRISM 3130xl Genetic Analyzer and chain termination method (Applied Biosystems, Carlsbad, CA). Genotype distribution and allele frequency was similar in CRC patients and controls individuals. We expect observe C and G allele in both groups but only was found C allele. In this study for first time we identified genetic distribution of exonic rs76189946 polymorphism in EGF gene both CRC patients and healthy controls. These results suggest there wasn't association between EGF polymorphism rs76189946 and risk of colorectal cancer in an Iranian population.
    Full-text · Article · Mar 2013 · Gastroenterology and hepatology from bed to bench
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    • "Melanoma B16 cells in the negative control group, the group transfected with p-VEGF, and the group given exogenous VEGF, EGF (epidermal growth factor), and CoCl2 [cobalt(II) chloride] were seeded in 24-well plates at a density of 1 × 104 cells/well. The EGF and CoCl2 treated groups were used for the reference and comparison of the effects of the exogenous VEGF and p-VEGF groups as both EGF and hypoxia (which can be mimicked by CoCl2 in vitro) were reported to promote the development and progression of melanoma [13, 14]. After 12, 24, 36, 48, and 60 h of incubation, 200 μl of 5 mg/l solution of MTT (Sigma, Guangzhou, China) in PBS was added to each well. "
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    Full-text · Article · Dec 2012 · Contemporary Oncology / Wspólczesna Onkologia
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